The fundamental goals of our work are to understand how eukaryotic cells regulate gene expression. Towards this end, we have focused our efforts on understanding how chromatin and chromatin modification enzymes particpate in gene regulation. These efforts will contribute to a larger effort to understand (and eventually manipulate) epigenetic regulation. At its most basic level, eukaryotic chromosomes contain information on multiple levels. The primary genetic information required for synthesis of most cellular components is encoded in the linear sequence of nucleotide bases incorporated into the DNA polymer. Eukaryotic chromosomes also encode additional information embedded in covalent modification of DNA itself or in the protein components of the chromosome. This information is critical for biological regulation of DNA transactions, including transcription, replication, recombination, and DNA repair. A major challenge for the current generation of biologists is to understand and interpret this 'Epigenetic Code.' Major unanswered questions regarding the epigenetic code include how the information is encoded and what biological systems are responsible for its deposition and for its interpretation. Further, the existence of such a code represents an outstanding opportunity for diagnostic and therapeutic efforts aimed at utilizing information from the Epigenetic Code to improve human health. Of particular interest to the NIEHS mission, it is highly likely that the epigenetic code is strongly impacted by the environment.